Shang, J, He, Q, Chen, Y, Yu, D ORCID: 0000-0002-8449-7725, Sun, L, Cheng, G, Liu, D, Xiao, J and Zhao, Z (2018) miR‐15a‐5p suppresses inflammation and fibrosis of peritoneal mesothelial cells induced by peritoneal dialysis via targeting VEGFA. Journal of Cellular Physiology. ISSN 0021-9541

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Abstract

Long‐term peritoneal dialysis (PD) often ends up with ultrafiltration failure (UFF) which is partially caused by persistent inflammation and fibrosis of peritoneal tissues. However, the mechanism is still unclear. In the current study, the peritoneum from UFF patients demonstrated inflammation and fibrosis which were positively related to the expression of vascular endothelial growth factor A (VEGFA). The in vitro model using human peritoneal mesothelial cells (HPMCs) stimulated by high glucose or advanced glycation end (AGE) product showed consistent changes of inflammation, fibrosis, and VEGFA. What's more, we showed that VEGFA was an instigator of inflammation and fibrosis. Several microRNAs (miRNAs) have been reported to regulate expression of VEGFA elsewhere. Five of them were selected to test the expression in the peritoneum of patients with PD. Results suggested that miR‐15a‐5p was the most significantly downregulated one. Also, in high glucose or AGE product‐stimulated HPMCs, miR‐15a‐5p decreased. When miRNA mimic was used to restore the expression of miR‐15a‐5p, high glucose‐induced VEGFA was repressed. The predicted binding site between these two molecules was confirmed by the dual‐luciferase assay. Restoration of miR‐15a‐5p restrained inflammation and fibrosis of HPMCs. TGF‐β1/Smad2 was shown to be the downstream signaling pathway and their activity was regulated by miR‐15a‐5p/VEGFA. In conclusion, our current study demonstrates that miR‐15a‐5p acts as a regulator of VEGFA mRNA and the following inflammation and fibrosis in peritoneal mesothelial cells. The miR‐15a‐5p/VEGFA pathway may be a potential target for preventing ultrafiltration failure in patients with PD.

Item Type: Article
Additional Information: This is the accepted author manuscript (AAM). The final published version (version of record) is available online via Wiley at https://onlinelibrary.wiley.com/doi/abs/10.1002/jcp.2766. Please refer to any applicable terms of use of the publisher.
Uncontrolled Keywords: fibrosis, inflammation, miR‐15a‐5p, peritoneal dialysis, vascular endothelial growth factor A
Subjects: R Medicine > R Medicine (General)
Divisions: Faculty of Medicine and Health Sciences > Primary Care Health Sciences
Depositing User: Symplectic
Date Deposited: 01 Nov 2018 13:59
Last Modified: 01 Nov 2018 14:00
URI: http://eprints.keele.ac.uk/id/eprint/5464

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